CA2074671A1 - Device and method for separating plasma from a biological fluid - Google Patents

Device and method for separating plasma from a biological fluid

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Publication number
CA2074671A1
CA2074671A1 CA 2074671 CA2074671A CA2074671A1 CA 2074671 A1 CA2074671 A1 CA 2074671A1 CA 2074671 CA2074671 CA 2074671 CA 2074671 A CA2074671 A CA 2074671A CA 2074671 A1 CA2074671 A1 CA 2074671A1
Authority
CA
Grant status
Application
Patent type
Prior art keywords
fluid
device
fluid flow
biological fluid
separation medium
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
Application number
CA 2074671
Other languages
French (fr)
Inventor
Thomas Bormann
Valdo Ivan Matkovich
Thomas Charles Gsell
David Boris Pall
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Pall Corp
Original Assignee
Pall Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date

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Classifications

    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01DSEPARATION
    • B01D61/00Processes of separation using semi-permeable membranes, e.g. dialysis, osmosis, ultrafiltration; Apparatus, accessories or auxiliary operations specially adapted therefor
    • B01D61/14Ultrafiltration; Microfiltration
    • B01D61/147Microfiltration
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/34Filtering material out of the blood by passing it through a membrane, i.e. haemofiltration, diafiltration
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/34Filtering material out of the blood by passing it through a membrane, i.e. haemofiltration, diafiltration
    • A61M1/3403Regulation parameters
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/36Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
    • A61M1/3601Extra-corporeal circuits in which the blood fluid passes more than once through the treatment unit
    • A61M1/3603Extra-corporeal circuits in which the blood fluid passes more than once through the treatment unit in the same direction
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01DSEPARATION
    • B01D63/00Apparatus in general for separation processes using semi-permeable membranes
    • B01D63/08Flat membrane modules
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2202/00Special media to be introduced, removed or treated
    • A61M2202/04Liquids
    • A61M2202/0413Blood
    • A61M2202/0415Plasma
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2202/00Special media to be introduced, removed or treated
    • A61M2202/04Liquids
    • A61M2202/0413Blood
    • A61M2202/0439White blood cells; Leucocytes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2205/00General characteristics of the apparatus
    • A61M2205/33Controlling, regulating or measuring
    • A61M2205/3331Pressure; Flow
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/14Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
    • A61M5/142Pressure infusion, e.g. using pumps
    • A61M5/145Pressure infusion, e.g. using pumps using pressurised reservoirs, e.g. pressurised by means of pistons
    • A61M5/1452Pressure infusion, e.g. using pumps using pressurised reservoirs, e.g. pressurised by means of pistons pressurised by means of pistons
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/14Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
    • A61M5/142Pressure infusion, e.g. using pumps
    • A61M5/145Pressure infusion, e.g. using pumps using pressurised reservoirs, e.g. pressurised by means of pistons
    • A61M5/148Pressure infusion, e.g. using pumps using pressurised reservoirs, e.g. pressurised by means of pistons flexible, e.g. independent bags
    • A61M5/1483Pressure infusion, e.g. using pumps using pressurised reservoirs, e.g. pressurised by means of pistons flexible, e.g. independent bags using flexible bags externally pressurised by fluid pressure
    • A61M5/1486Pressure infusion, e.g. using pumps using pressurised reservoirs, e.g. pressurised by means of pistons flexible, e.g. independent bags using flexible bags externally pressurised by fluid pressure the bags being substantially completely surrounded by fluid

Abstract

Abstract A device and method for increasing the platelet concentration of a biological fluid containing platelets by directing the biological fluid tangentially or parallel to the face of a separation medium such that a platelet-poor component of the biological fluid passes through the separation medium and a platelet-rich component of the biological fluid is recovered.

Description

h ~

P~VIOE: AND ~qETEIOD FOR SEP2~RATI:NG PI~SI~ l~ROM
BIC)If)GT~AL FL~Il:~

Technical Field The present in~ention concerns a devi e and 5 method for separating plasma from a biological fluid such as blood.

Backqround_of the Invention An adult human contains about 5 liters of blood, of which red blood cells account for about 45~ of the volume, white cells about 1~, and the balance being liquid blood plasma. Blood also contains large numbers of platelets, small detached fragments derive~d from the cortical cytoplasm of large cells callled megakaryocyte. A typical platelet i~ about 2-3 microns in diameter, lacks a nucleus, and has a life-span in circulating blood of less than 10 days. Its properties of adhesion and aggregation permit it to initiate hemostasis when vascular endothelium is damaged and also to initiate clottir.g to stop external bleeding.
The need for blood components is growing ~ 1 --rapidly as the th~rapeutic administratiQn of specific blood components increases. Blood bank personnel have responded to the increased need for blood components by attempting to increase packed red cell (PRC) and platelet concentrate (PC~ yields in a variety of ways. For example, donated blood is typically collected in a blood collection bag and separated by centrifugation into PRC and platelet-rich plasma (PRP) ~ractions, the latter of which is in current practice separated by a second centrifugation to provide plasma and PC. In separating the PRP from P~C, blvcd banX personnel have attempted to ensure that the entire PRP
fraction is rrcovered, but this has o~ten proved to be counterproductive, since the PRP, and the PC
subsequently extracted from it, are frequently con-taminated by red cells, giving a pink or red color to the normally light yellow PC. The presence o~
red cells in PC is so highly undesirable that pink or red PC is frequently discarded, or subjected to recentrifugation, both of which increase operating costs and are labor intensive.
The development of plastic blood collection bags ~acilitated the separation of donated whole blood into its various components, thereby making platelet concentrates available as a transfusion product. The separation of a single unit of donated whole blood, about 450 milliliters in United States practice, into its components is typically accomplished by use of di~ferential sedimentation.
A typ.ical procedure used in the United States utilizes a series of steps to separate donated blood into components, usually three components, each com-ponent having substantial therapeutic and monetary value. The procedure typically utilizes a blood collection bag whicll is integrally attached via flexible tubing to at least one, and preferably two or more, satellite bags.
A blood collection bag containing whole ~lood (with or without an anti-coagulank ~uch as citrate-phosphate-dextrose-adenine (CPDA-l)) i~ centrifuged (slow speed or ~oft-spin'l centrifugation) together with its sat~llite bags, thereby concentrating th~
red cells as PRC in the lower portion of the blood collection bag and leaving in the upper portion of the bag PRP, a suspension of platelets in the supernatant plasma (typically about 200-250 ml).
The PRP is then typically separated from the PRC by expression through a tube located at the top of the blood collection bag into a satellite bag.
The PRP-containing satellite bag, usually together with a second satellite bag, is then removed from the extractor and centrifuged at an elevated G force (high speed or "hard-spin"
centrifugation) with the time and speed appropriately adjusted so as to concentrate the platelets into the lower portion of the PRP bag.
When centrifugation is complete, the PRP bag contains sedimented platelets in its lower portion and clear plaæma in its upper portion.
The PRP bag is then placed in the plasma ex-tractor, and mos't of the clear plasma is expressed into a satellite bag, leaving the PRP bag containing only the sedimented platelets and about 50 ml of .
plasma; then in a subsequent step, this platelet composition is dispersed to make PC. The PRP bag, now containing ~ PC product, is then detached and stored for up to five days at room temperature (about 20- to 24C), until needed for a transfusion of platelets. For use with adult patients, the ~` ``t` ~
. 'f ~ ~ ' platele~s *rom ~ 10 donors are7 when required, pool=
ed for a single platelet transfusion, The plasma in the satellite bag may itself be transfused into a patient, or it may be sepaxated into a variety oP valuahle products~
Platelet concentrate can also be prepared using apheresis oP autologous blood. With ~hi~ method, whole blood is removed from a single donor, and centrifuged into its component parts. The platelets are then harvest~d and the remainder oP the blood is returned tQ the donor. This procedllre allows collection o~ multiple units from one donor.
Typically, a 2 to 3 hour apheresis proc~dure will produce a platelet product containing 3 x 1011 platelets, equi~alent to about six to ten units of random donor platelets, i.e., a typical transfusion unit. The common practice with respect to platelet concentrate is to transfuse a pool of six to ten units of platelets per administration, containing a total of about 300 to 700 ml of platelet concentrate.
The separation of the various blood components using centri~ugation is not without problems.
First, during th~e separation of PRP ~rom PRC, it is difficult to efficiently obtain th~ maximum yield of platelets while ]preventing red cells from entering the plasma. Secondly, when PRP is centrifuged to obtain a layer consi~ting principally of platelet~
concentrated at the bottom of the PRP-containing bag, the platelets so concentrated tend to form a dense aggregate which must be dispexsed in plasma to form plat~let concentrate~ The dispersion step is usually carried out by gentle mixing, Por example, by placing the ~ag on a moving table which rotates with a precessing tilted motion. This mixing 2 ~ 7 ~
requires several hours, which is an undesirable delay, and is believed by many researchers to produce a partially aggregated platelet concentrate.
It is further believed that the platelets may be damaged by the forces applied during centrifugation.
Finally, freshly donated blood contains platelets varying in age from newly formed to 9 days or more in age (platelet hal~-life is approximately 9 days). Newly formed platelets are larger, and are generally believed to be more active. Because the younger platelets are larger, they tend to sediment faster during the first centrifugation step, and consequently are present in larger numbers in the PRP nearest to the red cell interface. Thus, although it is desirable to reclaim a larger proportion of the younger, more actiye platelets, attempting to obtain a greater quantity poses a risk of contamination with red cellg.
In recovering platelets, it is desirable to restrict platelet loss to about 15% or less of the original platelet concentration. Platelets are notorious for being "stickyn, an expression reflecting the tendency of platelets suspended in blood plasma to adhere to any non-physiological surface to which they are exposed. Under many circumstances, they also adhere strongly to each other.
Platelets are also sensitivQ to a variety of environmental stimuli, one of which is temperature.
Whereas in blood banking practice other blood components are stored at 4-C or less in order to extend their useful lif~, platelets are best preserved at normal indoor ambient temperature, e.g.
20- to 24-C for a nominal useful life (in current United States practice) of about 5 days, although ~ ~ }

i ;' J ~

many physicians prefer to use them within 2 or 3 days of collection.
Recovery of platelets or a platelet concentrate may be adversely affected in several ways. As noted above, platelet-rich plasma is typically obtained by centrifuging a unit of donated whole blood and removing or isolating the P~P. Currently, platelet concentrate is obtained from the PRP by "hard-spin"
centrifugation ~rotating at about 5000 G). This hard-spin compacts the platelets into a pellet or concentrate at the bottom of the test tube, flask, or bag. ~he plasma component is then removed or expressed to a separate bag or container, leaYin~
the platelet concentrate component and some plasma behind~ This is labor intensive, and potentially damaging to the platelets because the hard-spin induces partial activation agglomeration of the platelets and may cause physiological damage. Such agglomeration requires several hours to resuspend the platelets in solution before they can be used for transfusion into a patient. Furthermore, the hard-spin typically produces "distressed" platelets which partially disintegrate upon resuspension~
Unfortunately, while mixing prevents agglomeration, encourages gas exchange by diffusion of oxygen through the walls o~ the bag (thereby controlling pH~, and bathes the product in needed nutrient~, this requires time, resulting in an increase in the number and size of microaggregates. Further, over time, gel-like bodies may be formed, which may comprise fibrinogen, degenerated protein, and degenerated nucleic acids. Thus, some platelets are lost due to the process conditions.
Furthermore, the transfusion of blood components which have not been leuco-depleted is not without risk to the patient receivin~ the transfusion. Some of these risks are detailed in U.S. Patent 4,923,620 and in U.S. Patent 4,880,548.
When leucocytes are removed from platelet-rich plasma, which typically results in the production of a leucocyte-frea platelet concentrate, the plat~let component of the filtrate usually passes through a filter or separation device. In these systems, platele~s may adhere to the ~urfaces of components of the separation device; such adhesion tends to cause ~ubstantial, and sometimes complete, removal of platelets from the filtrate. Furthermore, platelet concentrat~ present within the separation device at the completion of the separation process lh will be lost.
The following definitions are used in reference to the :nvention:
A) Biological Fluidr Biological fluids include any treat d or untreated fluid associated with living organisms, particularly blood, including whole blood, warm or cold blood, and stored or fresh blood; treated blood, such as blood diluted with at least one physiological solution, including but not limited to saline, nutrient, and/or anticoagulant solutions; one or more blood components, such as platelet concentrate (PC), platelet-rich plasma (PRP), platelet-poor plasma, platelet-free plasma, plasma, or packe!d red cells (PRC); analogous blood products derived from klood or a blood component or derived from hone marrow; red cells separated from plasma and resuspended in physiologica]. fluid, and platelets separated from plasma and reswspended in physiological fluid. The biological fluid may include leucocytes, or may ~e treated to remove leucocytes. Further, biological fluid refers to the }:

components described above and to similar or analogous klood products obtained by other means and with similar properties.
B) Unit of Whole Blood: Blood banks in the United States commonly draw about 450 millilit~rs (ml) of blood from the donor into a bag which contains an anti~oagulant to prevent the blood from clotting. However, the amount drawn differs from patient to patient and donation to donation~ ~erein the quantity drawn during such a donation is defined as a unit of whole blood.
C) Unit of Platelet-rich ~lasma (PRP) or Platelet Concentrate (PC): As used herein, a "unit"
is defined in the context of United States practice, and a unit of PRP, PC, or of platelets in physiological fluid or plasma is the quantity de-rived from one unit of whole blood or drawn during a single donation. Typically, the volume of a unit varies. Multiple units of some ~lood components, particularly platelets, may be pooled or co~bined, typically by combining six or more units.
D3 Plasma~Depleted Fluid: A plasma-depleted fluid refers to ,any biological fluid which has had some quantity of plasma removed therefrom, e.g., the platelet-rich fluid obtained when plasma is separated from PRP, or the fluid which remains after plasma is removed frvm whole blood.
E) Separation medium: A separation medium refer~ to a porous medium through which one or more biological fluids pass. As noted in more detail below, the porous medium for use with a biological ~luid may be formed from any natural or synthetic ~iber or from a porous or permeable membrane (or from other materials of similar surface area and pore. size) compatible with a biological fluid. The surface of the fibers or membrane may be unmodified or may be modified to achieve a desired property.
Although the separation medium may remain untreated, the fibers or membrane are preferably treated to make them even more effective for separating one component of a biological fluid, e.g., plasma, from other components of a biological fluid, e.g., platelets or red cells. The separation medium-is preferably treated in order to reduce or eliminate platelet adherence to the medium. Any treatment which reduces or eliminates platelet adhesion is included within the scope of the present invention. Furthermore, the medium may be surface modi~ied as disclosed in U.S. Patent 4,880,548, incorporated herein by reference, in order to increase the critical wetting surface tension (CWST) of the medium and to be less adherent of platelets.
Defined in terms of CWST, a preferred range of CWST
for a separation medium according to the invention 20 i8 above about 70 dynes/cm, more preferably above about 90 dynes/cm. Also, the medium may be sub~eated to gas plasma treatment in order to reduce platelet adhesion. Preferably, the critical wetting surface tension (cwæT) of the porous medium is within a certain range, as noted below and as dictated by its intended use. The pore surfaces of the medium may be modified or treated in order to achieve the desired CWST.
The porous medium may be pre-formed, multi-layered, and/or may be treated to modify the surface of the medium. If a fibrous medium is used, the fibers may be treated either before or after forming the fibrous lay-up. It is preferred to modify the fiber surfaces before forming the fibrous lay-up because a more cohesive, stronger product is ~` " ~

obtained after hot compression to form an integral filter element. The porous medium is preerably pre-formed.
~he porous medium may be configured in any suitable fashîon, such as a fl~t ~heet, a corrugated sheet, a web, hollow fibers, or a membrane.
F) Critical Wetting Surface Tension: As disclosed in U.S~ Patent 4,B80,548~ the CWST of a porous medium may be determined by individually applying to its sur~ace a series o~ li~uids with surface tensions varying by 2 to 4 dynes/cm and observing the absorption or non-absorption of each liquid over kime. The ~WST of a porous mediumy in units of dynes/cm, is defined as the mean value of the surface tension of the liquid which is absorbed and that of the liquid of neighboring surface tension which is not nbsorbed within a predetermined amount of time. The absorbed and non-absorbed values depend principally on the surface ~0 characteristiGs of the material from which the porous medium is made and secondarily on the pore size characteristics of the porous medium.
Liquids with surface tensions lower than the CWST of a porous medium will spontaneously wet the medium on contact:, and, if the pores of the medium are interconnected, liquid will flow through the medium readily. Liquids with surface tensions higher than the C`WST of the porous medium may not flow at all at low differential pressure~ or may flow unevenly at sufficiently high differential pressures to force the liquid through the porous medium. For example, the porous medium which is used to process PRP, it is preferred that the CWST
be held within a range above about 70 dynes/cm. For the porous medium which is used to process whole ~` " ~

blood, it is prefexred that the CWST be held within a range above about 53 dyn~s~cm.
G) Tangential flow filtration: As used hexein, tangential flow filtration refers to passing or circulating a biological fluid in ~ genera~ly parallel or tangential manner to the surface of the separa'_ion mediumu Summary of the Invention The invention involves the treatment of a bîological fluid to non-centrifugally separata a~
least one component from the biological fluid, e.g., treatin~ PRP to obtain pla~ma and PC, or separating plasma from whole blood. Proces~es and devices according to the invention utilize a s~paration medium that allows the passage of one component of ~he biological fluid, ~uch as plasma, ~ut prevents passage of other components, such as platelets or red cells, through the medium, thereby eliminating the need for "hard-spin" centrifugation as a processing step. Tangential flow o~ a biological ~luid parallel to the upstream surface of the separating medium permits the passage of p~asma through the medîum, while reducing the tendency f~r cellular components or platelets to adhere to the surface of the m.edium, thus assisting in the prevention of passage of platelets through the ~eparation medium. The hydrodynamics of ~low parallel to a surface are indeed believed to be such that during flow parallel to the surface, platelets develop a spin which causes them to be recovered from the surface.
~ he device and method of the present invsntion thus protect platelets and red blood cells from physiological damage, and directly and effectively f'J"~I ~; A~
minimize or eliminate loss or damage caused by the currently used centrifugal separation processes~ by reducing the exposure to harmful centrifugation.
Furthermore, the platelets and/or red blood cells are not required to pass ~hrough yet another filtration device in order to be separated from ~RP.
A feature of the ~eparation device of the invention, therefore, is the increased yield of clinically and therapeutically superior platelet concentrate and/or platelet-free (or platelet~poor) plasma.
~ dvantageous features of the devices and methods of the present invention include the separation of at least one component of a biological fluid from the rest of the fluid with minimal loss or activation of platelets. Platelet function is believed to be only minimally affected by the separation process, and platelet survival time within the patient is believed to be significantly longer. Further, because of the high cost and increased demand for both platelet preparations and ~or plasma, as well as the clinical need to deli~er a maximum ~herapeutic dose, a device according to the invention can deliver a higher proportion of the platelets or plasma originally present in the sample. Such a device is an object of this invention. It is also an object of the present invention to rec~laim a larger proportion of the youngert more active platelets in a sample~
It is yet another object of this invention to provide a device and method for separating platelet-poor plasma or platelet-free plasma from a biological ~luid~ such as PRP or from whole blood, without requiring rotation, spinning, or centrifugation to effect the separation~ Yet another object of the present in~ention is to provide for maximum recovery of plasma from whole blood or from PRP.
Another object of this invention is to reduce or eliminate of the labor required for ~entrifugation, concomitant with elimination of damage to platelets during hard-spin centrifugation~

Brief Description_of the Drawi~as Figure 1 is an elevation of an embodiment of ~e presè~ ~n~en~ ~n.
Figure 2 is a cros~-section o~ an embodiment of the invention, showi~g the ~irst fluid flow path in a ~eparation device according to the invention.
Figure 3 is a section of Figure 2, along A-~A.
Figure 4 is a section of Figure 2, along B-~B.
Figure 5 is a cross-section of an embodiment of the invention, showing the second fluid flow path in a separation device according to the invention.
Figure 6 is a section of Figure 5, along C~
Figure 7 is a section of Figure 5, along D--D.

Description of the Preferred Embodiment~
The present invention involves the separation of one or more components from a biological fluid.
In accordance w,ith the present invention, a biological fluicl, particularly blood, is exposed to a separation medium suitable for passing at least one component of the biological fluid, pa~ticularly plasma, there~hrough, but not other component~ of the biological fluid, particularly platelets and/or red cell~. Clogging of the separation medium by these other components i$ minimized or prevented~
As ~hown in Figure 1, a preferred separation device of the present invention comprises a housing 0 having first and second portions lOa, lOb joined : ` ` ~

in any convenient manner. For example, the first and second housing portions lOa, lOb may be ~oined by means of an adhesive, a solvent, or one or more connectors. ~he housing 10 also has an inlet 11 and first and second outlets 12 and 13, respectively, such that a first fluid flow path 14 i6 established between the inlet 11 and first o~tlet 12 and a second fluid flow path 15 is established between ~he inlet 11 and the second outlet 13c A separation medium 16 having first and second surface~ 15a, 16b i5 positioned inside the housing 10 between the first and second housing portions lOa~ lOb.
Further, the separation medium 16 is positioned parallel to the first fluid flow path 14 and across the second fluid flow path 15.
Embodiments of the present invention may be configured in a variety of ways to ensure maximlum contact of the biological fluid with the first surface ~6a of separation medium 16 and to reduce or eliminate clogging on the first surface 16a of the separation medium. For ~xample, the separation device may include a ~irst shallow chamber facing the first surface 16a of the separation medium 16~
The first chamber may include an arrangement of ribs which spread the flow of biological fluid over the entire first surface 16a of the separation me~ium 16. Alternatively, the first chamber may include one or more chalmels, grooves, conduits, passages, or the like which may be serpentine, parallel, curved, or a variety of other con~igurations.
The fluid flow channels may be of any suitable design and construction. For example, the channels may have a rectangular, triangular, or semi-circular cross section and a constant depth. Pre~era~ly~ the channels have a rectangular cross section and vary in depth, for example, between inlet 11 and outlet 12.
In the embodiment shown in Figures 2, 3, and 4, the inlet 11 of the housing 10 is connect~d to serpentine fluid flow channels ~0, 21~ and 22 which face the first surface 16a of the separation m~dium 16. These channels 20-22 separate ~he inlet flow of biological ~luid into separate flow paths tangential to the fixst surface 16a of the separation medium 16. Extending along the first surface 16a, the serpentine fluid flow channels 20~ 21, and 22 may be recombined at first outlet 12 o~ ~he housing 10.
Embodiments of the present invention may also be configured in a variety of ways to minimize back pressure across the separation medium 16 and to ensure a sufficiently high velocity of flow to the second outlet 12 to pre~ent fouling o~ surface 16a, while minimi~ing hold~up volume. The separation device includes a second shallow chamber facing the 20 second surface 16b of the separation medium 160 Like the first chamber, the second chamber may include an arrangement of ribs or may comprise one or more channels, grooves, conduits, passages, or the like which may be serpentine, parallel, curved, or have a variety of other configurations.
The fluid flow channels may be of any suitable design and construction. For example, the channels may have a rectangular, semi-circular, or triangular cross section and a constant or variable depth. In the embodiment shown in Figures 5-7, several serpentine fluid flow ahannels 31, 32, 33, 34, and 35 face the second surface l~b o~ the separation medium 16. Extending along the second surface 16b, the serpentine fluid flow channels 31-35 may be recombined at the second outlet 13.

7 ~

Ribs, walls, or projections 41f 42 may ~e used to define the channels 20-22, 31-3~ of the first and second chambers and/or may support or position the separation medium 16 within the housing 10. In a preferred embodiment of the invention, there are more walls 42 in the second chamber than in the first chamber to prevent deformation of the separation medium 16 caused by pressure differential through the separation medium.
In use, a biological fluid, e.g., whole blood or PRP, is fed under sufficient pressure into the - inlet 11 of housing 10 from any suitable source of the biological fluid. For example, the biological fluid may be injected from a syringe into the inlet 11 or it may be forced into the inlet 11 from a flexible bag using a gravity head, a pressure cuff, or an expre~sor. From the inlet 11, the biological fluid enters the channels 20-22 of the first chamber and passes tangentially or parallel to the first surface 16a of the separation medium 16 on the way to the first outlet 12 via the first fluid flow path 14. At least one component of the biological fluid, e.g., plasma, passes through the separation medium 16, enters the channels 31-35 of the second chamber, and is directed toward the second outlet 13 via the second fluid flow path 15. As the biological fluid continues along the first flow path 14 tangentially or parallel to the first surface 16a of the separation medium 16, more and more plasma crosses the separation medium 16. A pla~ma-depleted fluid then exits the housing 10 at the first outlet 12 and is recovered in one container 17 while plasma exits the housing 10 at the second outlet 13 and is recovered in another container 18.
While any biological fluid containing plasma r ~ ,,. . " , may be used in conjunction with the present invention, the present invention is particularly well-suited for use with blood and blood products, especially whole blood or PRP. By subjecting PRP to processing in accordance with the present invention, PC and platelet-free plasma may be obtained without centrifugation of the PRP and the attendant disadvantages discussed aboveq Likewise, platelet-free plasma may be obtained from whole blood. The biological fluid may be supplied in any suitable guantity consistent wi~h the capacity of the overall device and by any suitable means, e.~., in a batch operation by, for example, a blood bag connected to an expressor or a syringe, or in a continuous operation as part of, for example, an apheresis system. Exemplary sources of biological fluid include a syringe 19, as shown in Figure 1, or a biological fluid collection and processing ~y~tem such as that disclosed in U.S. Serial No.
20 07/609,654, filed November 6, 1990, incorporated herein by reference. A source of biological fluid may also include an apheresis system, and/or may include a system in which biological fluid is recirculated through the system.
The housing and the separation medium of the present in~entive device may, of course, be of any suitable configuration and material. While the prefexred device has one inlet and two outlets, other configurations can be employed without adversely affecting the proper functioning of the device. For ~xample, multiple inlets for a biological fluid may be used so long as the biological fluid flows tangentially to the face of the separation mediumu The plasma may preferably be stored in a region separated from the separation medium in order to avoid possible reverse flow of the plasma bac~lc across the separation medium to the plasma-depleted fluid.
The separation medium and housing may be of any 5 suitable material and confi~uration and the ~eparation medium may be arranged in the present inventive device in any suitable manner so long as the biological iEluid flow tangential or parallel to the separation medium i~; maintained to a sufficient 10 extent to avoid or minimize substantial platelet adhesion to the separation membrane. one ~killed in the art will recognize that platelet adhesion may be controlled or affected by manipulating any vf a number of factors: velocity of the fluid flow, configuration o~ the channel, depth of the channel, varying the depth of the channel, the surface characteristics of the sepaxation medium, the smoothness of the medium's sur~ace, and/ox the ~ngle at whioh the fluid flow crosses the face of the separation medium, among other factors. For example, the velocity of the first fluid flow is preferably sufficient to remove platelets from the surface o~ the s,eparation medium. Without intending to be limited thereby, a velocity in excess of about 30 cm/second has been shown to be adequate.
The velocity of the fluid flow may also be affected by the volume of the biological fluid, by varying the channel depth, and by the channel width.
For example, the channel depth may be varied from about .25 inch to about .001 inch, as shown in Figure 3. one skîlled in the art will recognize that a desired velocity may be achieved by manipulating these and other elements. Also, platelets may not adhere as readily to a separation medium having a smooth surface as compared to a ' S ` ~

membrane having a rougher surface.
In accordance with the invention, the separation medium comprises a porous medium suitable for passing plasma therethrough. The separation medium, as used herein, may include but is not limited to polymeric fibers (including hollow fibers), polymeric fiber matricesr pol~meric membranes, and solid porous media. Separation media accordi~g to the inve~tion remove plasma from a biological solution containing platelets, t~pically whole blood or PRP, without removing proteinaceous blood components and without allowing a substantial amount of platelets to pass therethrough.
A separation medium, in accordance with the invention, preferably exhibits an average pore rating generally or intrinsically smaller than the average size of platelets, and, preferably, platelets do not adhere to the surface of the separation medium, thus reducing pore blockage. The separation medium should also have a low affinity for proteinaceous components in the biological ~luid such as PRP. This enhances the likelihood that the platelet-poor solution, e~g., platelet-~ree plasma will exhibit a normal concentration of proteinaceous clotting factors, growth factors, and other needed components.
For the separation of about one unit of whole blood, a typical ~eparation device according to the invention may include an effective pore size smaller than platelets on the averager typically less tha-n about 4 micrometers, prefer~ly less than about 2 micrometers. The permeability and size of the separation device is preferably sufficient to produGe about 160 cc to about 240 cc of plasma at reasonable pressures ~e.g., less than about 20 psi) in a r~asonable amount of time (e.g., less than about one hour~. In accordance with the invention, all of these typical parameters may be varied to achieve a desired result~ i.e~, varied pre~erably to minimize platelet loss and to maximize platelet-free plasma production.
In accordance with the invention, a separation medium formed of fibers may be continuous, staple, or melt blown. The fibers may be made from any material compatible with a biological fluid containing platelets, e.g., whole blood or PRP, and may be treated in a variety o~ ways to make the medlum more effective. Also, the fiberfi may ~e bonded, fused, or otherwi~e fixed to one another, or they may simply be mechanically entwined. A
separation medium formed of a me~brane, as the term is used herein, refers to one or more porous polymeric sheets, such as a woven or non-woven web of fibers, with or without a flexible porous ~ubstrate, or may compri~e a membrane formed from a polymer solution in a solvent by precipitation of a polymer when the polymer solution is contacted by a solvent in which the polymer is not soluble. The porous, polymeric sheet will typically have a substantially uniform, continuous matrix structure containing a myriad of small largely interconnected pores.
The separation medium of this invention may be formed, for example, from any synthetic polymer capable of forming fibers or a membrane. While not necessary to the apparatus or method of the invention, in a preferred embodiment the polymer is capable of serving as a substrate for grafting with ethylenically unsaturated monomeric materials.
Preferably, the polymer should be capable of `i ~

J ~ , ~ , 3 reacting with at least one ethylenically unsaturated monomer under the influence of ionizing radiation ox other activation means without the matrix being adversely affected. Suitable polymers fsr use as S the substrate include, but are not limited to, polyolef.ins, polyesters, polyamides, polysulfones, polyarylene oxide~ and sulfides, and polymers and copolymers ~ade from halogenated olefins and unsaturated nitriles. Preferred polymers are polyolefins, polyesters, and polyamides, e.g., polybutylene terephthalate (PB~ and nylon. In a preferred embodiment, a polymeric membrane may be formed from a fluorinated polymer ~uch as polyvinylidene difluoride (PVDF~. The most preferred separation media are a microporous polyamide membrane or a polycarbonate membranG.
Surface characteristics of a fiber or membrane can be modified by a num~er of methods, for example, by chemical reaction including wet or dry oxidation, by coating the surface through deposition of a polymer thereon, by grafting reactions which are activated by exposure to an energy source ~uch as heat, a Van der Graff generator, ultraviolet light, or to various other forms o~ radiation, and by treatment of the fibers or membrane with a gas plasma. The preferred method is a grafting reaction using gamma-radLati.on, for example, from a cobalt source.
Radiation grafting, when carried out under appropriate conditions, has the advantage of considerable flexibility in the choice of reactants, surfaces, and in the methvds for activating the required reaction. Gamma-radiation grafting is particularly preferable because the products are very stable and have undetectably low aqueous ~5 ~ ~ r~ r ~i extractable levels. Furthel~3re, the ability to prepare synthetic organic fibrous media having a CWST within a desired range is more readily accomplished using a gamma radiation grafting technique.
An exemplary radiation grafting technique employs at least one of a variety of monomers each comprising an ethylene or acrylic moie~y and a second group, which can ~e selected from hydrophilic groups (e-.g., -COOH, or -OH) or ~ydrophobic groups ~e.g., a methyl group or saturated chains such a~
-CH2CH2CH3). Grafting of the fiber or membxane surface may also be accomplished by compounds containing an ethylenically unsaturated group, such as an acrylic moiety, combined with a hydroxyl group, such as, hydroxyethyl methacrylate ~EMA).
Use of HEMA as the monomer contributes to a very high CWST. Analogues with similar characteristics may also be used to modify the surface aharacteristics of ~ibers.
It has been observed that porous media surface treated using some grafting monomers or combinations of monomers behave differently with respect to the span between the surface tension of the liquid which is absorbed and the surface tension of the liquid which is not absorbed when determining the CWST.
~his span can vary from less than 3 to as much as 20 or more dynes/cm. Preferably, the media has a span between the absorbed and non-absorbed values of about 5 or fewer dynes/cm. This choice reflects the greater precision with which the CWST can be controlled when narrower spans are selected, albeit media with wider spans may also be used. The use cf the narrower span is preferred in order to improve product quality control.

Radiatioll grafting may increase fiber to-fiber bonding in a fibrous medium. Consequently, a fibrous medium which exhibits little or no fiber-to-fiber bonding in an untreated state m y 5 axhibit significant fiber-to-fiber bonding after the fibers have been radiation grafted to increase the CWST of the medium.
In accordance with an e~bodiment of the invention, the separating medium may be surface-modified, typically by radiation graftingO in orderto achieve the desired performance characteri~tics, whereby platelets are concentrated with a minimum of medium blocking, and whereby the resulting plasma solution contains essentially all of its native proteinaceous constituent~. Exemplary membranes having a low affinity for proteinaceous substances are disclosed in U.S. Patents 4,886,83~: 4,906~374;
4,964,9~9; and 4,968,533, all incorporated herein by reference.
Suitable mel~branes in accordance with an embodiment of the invention may be microporous membranes and may be produced by a solu~ion casting method.
As noted above, establishing a tangential flow of the biologica:L fluid being processed parallel with or tangential to the face of the separation medium minimizes platelet collection within or passage through the separation medium. In accordance with the invention, the tangential flow can be induced by any mechanical configuration of the flow path which induces a high local fluid velocity at the immediate membrane surface. The pressure driving the biological fluid across the separation medium may be derived by any suitable means, for example/ by gravity head or by an ~ 23 -., 1 ~

~.; . ;, ~s L . ~, j expressor O
The tangential flow of the biological fluid may be directed tangential or parallel to the face of the separation medium in any suitable manner, pre~erably utilizing a substantial portion of the separation medium surIace while maintaining a sufficient flow to ensure that the platelets do not clog or block the pore~ of the separation medium~
The flo~ of the biological fluid is preferably directed ~angentially ox parallel to the face of the separation medium through use of at least one serpentine fluid flow channel which is designed to maximize utilization of the ~eparation medi~m, ensure a suff iciently total area contact between the biological fluid and the separation medium, and maintain a suffici.ent flow of biological fluid to minimize or prevent platelet adhesion to the separation medium. Most preferably, several (eOg., three or more~ fluid flow channels are utilized so as to fix the separation medium in place and to prevent sagging of the membrane due to the applied pressure. The fluid flow channels may be of any suitable design and construction and preferably are variable with respect to depth such as depth to maintain optimal pressure and fluid flow across the face of the separation medium. Fluid flow channels may also be utiliLzed on the side of the separation medium opposite 1:he biological fluid tangential flow to control the flow rate and pressure drop of a platelet-poor ~luid, such as plasma.
A system according to the present invention may be used in con~unction with other functional biomedical devices, including filtration and/or separation devices, e.g., a device for removing leucocytes from a platelet-containing solution or concentrate. Exemplary devices are disclosed in U.S. Patent ~,880,548, and U.S. Patent 4,925,572 incorporated herein by reference in their entirety.
A functional biomedical device, as used herein, refers to any of a number of devices, assemblies, or systems used in the collection and/or processing of biological fluids, such as whole blood or a blood component. Exemplary functional biomedical devices include biologîcal fluid containers, ~uch as collection, transfer, and storage bags; conduits and connectors interposed between the containers:
clamps, closures, and the like; air or gas inlet or outlet devices, a de~ubbler; a pump and a red cell barrier device or assembly. The functional biomedical device may also include a device for destroying biological contaminants, such as a high intensity light wave chamber, or a device for sampling a biological fluid.
The present inventive device may similarly be part of an apheresis systemO The biological fluid to be processed, the platelet-rich solution, and/or the platelet-poor solution may ke handled in either a batch or continuous manner. The sizes, nature, and configuration of the present inventive device can be adjusted to vary the capacity of the device to suit its intended environment.
-In order that the invention herein describedmay be more fully understood, the following examples are set out regarding use of the present invention.
These examples are for illustrative purposes only and are not to be construed as limiting the present invention in any manner.

Examples Whole blood was collected into an Adsol~ donor set and was processed under standard conditions to yield a unit of PRP. ~he PRP was then filtered to remove leucocytes using a filter device described in U.S. Patent 4,880,548. The xemoval efficien~y was >99.9%.
The filtered PRP unit was then placed in a pressure cuff to which a pres~ure of 300 mm Hg was applied. -The tubing exiting the bag ~clamped closed at this point) was connected to the inlet port of a separation device as shown in Figures 1, 2, and ~.
A microporous polyamide membrane having a pore rating o~ 0. 65 microns was used as the separation medium in the device. The area of the membrane was about 17.4 square centime~.ers. The depth of the first fluid flow path cha~nels decreased from about 0. 03 cm near the inlet to about 0.01 cm near the outlet. The depth of the second fluid flow path channels was about 0.025 cm~ The outlet ports of the device were connected to tubing which allowed the volume of fluid exiting the device to be measur4d and saved for analysis.
The test of the present invention was started by opening the clamp and allowing PRP to enter the device. Clear fluid (plasma) was observed to exit one port, and turbid fluid (platelet concentrate~
exited the other port. The duration of the test was 42 minutes, during which 154 ml of plasma and 32 ml of platelet concentrate was collected. The concentration of platelets in the plasma was found to be 1.2 x 104/~l, while the concentration of platelets in the platelet concentration was found to be 1.43 x 106/~l.
The above results indicate that PRP can be - 2~ -!~! ~;

concentrated to a useful level, and platelet-poor plasma recovered, in a reasonable time by a d~vice accordin~ to the invention.

EXAMPLE 2.

A sample of 4~0 ml of whole blood was collected under standard conditions from a human donor and placed in a typical flexible plastic blood bag. ~n analysis of the whole blood ~ample indicates that i~
contained about 203 ml plasma. A 2 cc whole blood sample was withdrawn from the bag in a 5 cc syringe and attached to the inlet port of a device constructed in accordance with the invention.
The present inventive device included a serpentine fluid flow path with a channel length of 15 32.5 cm, a constant width of 0.~13 cm, and a constant depth of 0.127 cm. The fluid flow path was of a "C" cross~section and, on its open side, contacted a microporous polycarbonate membrane having a pore rating of 0.4 microns which served as the separation medium. About 26.4 cm2 of the microporous membrane were thereby part of the fluid flow path and were capable of being contacted by the whole blood sample or processed fluid as it passed through the device in the fluid flow path. Fluid flowed through the separation medium at a rate of 0.2 ml/min. The entire whole blood sample was processed in about 2 minutes. Air in the syringe was used to drive any hold-up through the device.
At the conclusion of the processing, a total of about 1.6 cc of turbid fluid (red cell containing fraction) and .4 cc of clear fluid was collected from the processing of the whole blood sample. An analysis of the clear fluid indicated that it was :~` ~

plasma.
The above results indicate that plasma can be removed from whole hlood in a reasonable ~ime through the use of the present inventionO

EXAMPLE 3.
A sample of 450 ml of whole blood is collected under standard conditions from a human donor and placed in a typical flexible plastic blood ~ag. An analysis of the whole blood sample indicates that the hematocrit is 37%, indicating that the sample includes about 283.5 cc plasma and 166.5 cc red cells. A 2 cc whole blood sample is withdrawn from the bag in a 5 cc syringe and attached to the inlet port of a device comprising a serpentine fluid flow path similar to that described in Example 2.
At the conclusion of the processing a total of about .75 cc of turbid fluid (red cell containing fraction) and 1.25 cc of clear fluid is collected from the processing of the whole blood sample. An analysis of the clear fluid indicates that it is plasma.
The above results indicate that plasma can be efficiently removed from whole blood in a reasonable time through the use of the present invention.
_ _ While the invention is susceptible to various modifications and alternative forms, certain specific embodiments thexeof have been described herein. It should be understood, however, that this description and the examples of the present invention set out above are not intended to limit the invention to the particular embodiments disclosed, but, on the contrary, the intention is to cover all modifications, equivalents, and 5~ 7 ~' alternatives falling within the spirit and scope of the invention.

2g

Claims (35)

1. A device for removing a plasma from a biological fluid comprising:
a housing having an inlet and first and second outlets and defining a first liquid flow path between the inlet and the first outlet and a second liquid flow path between the inlet and the second outlet; and a separation medium positioned inside the housing tangentially to the first flow path and across the second flow path, the separation medium being suitable for passing a plasma component of the biological fluid therethrough.
2. The device of claim 1 wherein said separation medium comprises a porous membrane.
3. The device of claim 1 wherein said first fluid flow path comprises at least one fluid flow channel.
4. The device of claim 3 wherein said fluid flow channel is a serpentine fluid flow channel.
5. The device of claim 4 wherein said first fluid flow path comprises two or more fluid flow channels.
6. The device of claim 1 wherein said second fluid flow path comprises at least one serpentine fluid flow channel.
7. The device of claim 6 wherein said second fluid flow path comprises five fluid flow channels.
8. The device of claim 3 wherein said fluid flow channel or channels are configured to maintain substantially constant velocity of the biological fluid passing therethrough.
9. The device of claim 3 wherein said fluid flow channel is deeper near the inlet than near the first outlet.
10. The device of claim 3 wherein said fluid flow channel decreases in depth over the length of the channel in the fluid flow direction.
11. The device of claim 1 wherein said biological fluid is platelet-rich plasma, said platelet-poor component is plasma, and said platelet-rich component is platelet concentrate.
12. The device of claim 1 wherein said biological fluid is whole blood and said platelet-poor component is plasma.
13. A device for processing a biological fluid comprising:
a housing having a first portion and a second portion;
an inlet and a first outlet in the first portion and a first fluid flow path therebetween;
a second outlet in the second portion and a second fluid flow path between the inlet and the second outlet;
a separation medium positioned inside the housing between the first portion and the second portion and tangentially to the first flow path and across the second flow path, the separation medium being suitable for passing a plasma component of the biological fluid therethrough but not a platelet rich component of the biological fluid.
14. The device of claim 13 wherein said first fluid flow path comprises at least one fluid flow channel.
15. The device of claim 14 wherein said fluid flow channel is a serpentine fluid flow channel.
16. The device of claim 15 wherein said first fluid flow path comprises three fluid flow channels.
17. The device of claim 13 wherein said second fluid flow path comprises at least two serpentine fluid flow channels.
18. The device of claim 17 wherein said second fluid flow path comprises five fluid flow channels.
19. The device of claim 13 wherein the fluid flow channel or channels are configured to maintain substantially constant velocity of the biological fluid passing therethrough.
20. The device of claim 13 wherein said fluid flow channel decreases in depth over the length of the channel in the fluid flow direction.
21. A device for treating a biological fluid comprising:
a separation medium having first and second external surfaces and being suitable for passing a plasma component of the biological fluid; and a housing defining first and second flow paths, the separation medium being disposed within the housing wherein the first flow path extends tangentially to the first external surface of the separation medium and the second flow path extends from the first external surface through the separation medium to the second external surface.
22. A system for processing a biological fluid comprising:
a housing having an inlet and first and second outlets and defining a first liquid flow path between the inlet and the first outlet and a second liquid flow path between the inlet and the second outlet;
a separation medium positioned inside the housing tangentially to the first flow path and across the second flow path, the separation medium being suitable for passing a plasma component of the biological fluid therethrough but not a platelet-rich component of the biological fluid;
a first container in fluid communication with the first outlet; and a second container in fluid communication with the second outlet.
23. A method for decreasing the plasma content of a biological fluid comprising:
directing a biological fluid through the device of claim 1 tangentially to the surface of the separation medium whereby a platelet-poor component of the biological fluid passes through the separation medium and a platelet-rich component of the biological fluid is recovered.
24. The method of claim 23 further comprising directing the biological fluid tangentially to the surface of the separation medium at substantially constant velocity.
25. The method of claim 23 wherein said separation medium comprises a porous membrane.
26. The method of claim 25 further comprising directing the biological fluid tangentially to the surface of the porous membrane at substantially constant velocity.
27. The method of claim 23 wherein said biological fluid passes through at least one fluid flow channel tangentially to the surface of the separation medium.
28. The method of claim 27 wherein said fluid flow channel is a serpentine fluid flow channel.
29. The method of claim 28 wherein said biological fluid passes through three serpentine fluid flow channels tangentially to the surface of the separation medium.
30. The method of claim 23 wherein said biological fluid is platelet-rich plasma, said platelet-poor component is plasma, and said platelet-rich component is platelet concentrate.
31. The method of claim 23 wherein said biological fluid is whole blood and said platelet-poor component is plasma.
32. The method of claim 27 wherein a platelet-poor component is recovered.
33. The method of claim 27 wherein a platelet-rich component is recovered.
34. The method of claim 23 wherein biological fluid is recirculated through the separation medium.
35. A method of treating a biological fluid comprising:
directing the biological fluid through the device of claim 1 tangentially to a first exterior surface of the separation medium; and passing a plasma component of the biological fluid through the separation medium to a second exterior surface of the separation medium.
CA 2074671 1991-11-04 1992-07-27 Device and method for separating plasma from a biological fluid Abandoned CA2074671A1 (en)

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